Risk Factors for the Development of Psoriasis

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Abstract

Psoriasis is an immune-mediated genetic skin disease. The underlying pathomechanisms involve complex interaction between the innate and adaptive immune system. T cells interact with dendritic cells, macrophages, and keratinocytes, which can be mediated by their secreted cytokines. In the past decade, biologics targeting tumor necrosis factor-α, interleukin (IL)-23, and IL-17 have been developed and approved for the treatment of psoriasis. These biologics have dramatically changed the treatment and management of psoriasis. In contrast, various triggering factors can elicit the disease in genetically predisposed individuals. Recent studies suggest that the exacerbation of psoriasis can lead to systemic inflammation and cardiovascular comorbidity. In addition, psoriasis may be associated with other auto-inflammatory and auto-immune diseases. In this review, we summarize the risk factors, which can be divided into two groups (namely, extrinsic and intrinsic risk factors), responsible for the onset and exacerbation of psoriasis in order to facilitate its prevention.

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Obesity in autoimmune diseases: not a passive bystander.

Mathilde Versini, Pierre-Yves Jeandel, Eric Rosenthal … (2014)

In the last decades, autoimmune diseases have experienced a dramatic increase in Western countries. The involvement of environmental factors is strongly suspected to explain this rise. Particularly, over the same period, obesity has followed the same outbreak. Since the exciting discovery of the secretory properties of adipose tissue, the relationship between obesity and autoimmunity and the understanding of the underlying mechanisms have become of major interest. Indeed, the fat tissue has been found to produce a wide variety of "adipokines", involved in the regulation of numerous physiological functions, including the immune response. By conducting a systematic literature review, we extracted 329 articles regarding clinical, experimental and pathophysiological data on the relationship between obesity, adipokines - namely leptin, adiponectin, resistin, visfatin - and various immune-mediated conditions, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), multiple sclerosis (MS), type-1 diabetes (T1D), psoriasis and psoriatic arthritis (PsA), and thyroid autoimmunity (TAI), especially Hashimoto thyroiditis (HT). The strongest levels of evidence support an increased risk of RA (OR=1.2-3.4), MS (OR=2), psoriasis and PsA (OR=1.48-6.46) in obese subjects. A higher risk of IBD, T1D and TAI is also suggested. Moreover, obesity worsens the course of RA, SLE, IBD, psoriasis and PsA, and impairs the treatment response of RA, IBD, psoriasis and PsA. Extensive clinical data and experimental models demonstrate the involvement of adipokines in the pathogenesis of these autoimmune diseases. Obesity appears to be a major environmental factor contributing to the onset and progression of autoimmune diseases.

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Prevalence of cardiovascular risk factors in patients with psoriasis.

Andrea L. Neimann, Daniel B. Shin, Xingmei Wang … (2006)

Previous studies suggest that patients hospitalized for psoriasis have an increased frequency of a variety of cardiovascular comorbidities. Limited population-based data exist on this association, and few studies have determined which factors are independently associated with psoriasis. We sought to determine whether the prevalence of the major cardiovascular risk factors was higher in mild and severe psoriasis than in patients without psoriasis. We conducted a population-based study in the United Kingdom using the General Practice Research Database. Patients were classified as having severe psoriasis if they received a code for psoriasis as well as systemic therapy. Patients were defined as having mild psoriasis if they ever received a psoriasis code but no systemic therapy. Control subjects were selected from the same practices and start dates as psoriasis patients. Patients were classified as having risk factors if they received codes for diabetes, hypertension, hyperlipidemia, obesity, or smoking. Analyses were performed by using conditional logistic regression, and adjustments were made considering age, gender, person-years, and all cardiovascular risk factors. We identified 127,706 patients with mild psoriasis and 3854 with severe psoriasis. Respective prevalence rates of risk factors in those with severe psoriasis, mild psoriasis, and in controls were as follows: diabetes (7.1%, 4.4%, 3.3%), hypertension (20%, 14.7%, 11.9%), hyperlipidemia (6%, 4.7%, 3.3%), obesity (20.7%, 15.8%, 13.2%), and smoking (30.1%, 28%, 21.3%). Patients with mild psoriasis had a higher adjusted odds of diabetes (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.08-1.18]), hypertension (OR, 1.03; 95% CI, 1.01-1.06), hyperlipidemia (OR, 1.16; 95% CI, 1.12-1.21), obesity (OR, 1.27; 95% CI, 1.24-1.31), and smoking (OR, 1.31; 95% CI, 1.29-1.34) than controls. Patients with severe psoriasis had a higher adjusted odds of diabetes (OR, 1.62; 95% CI, 1.3-2.01), obesity (OR, 1.79; 95% CI, 1.55-2.05), and smoking (OR, 1.31; 95% CI, 1.17-1.47) than controls. Additionally, diabetes (OR, 1.39; 95% CI, 1.22-1.58) and obesity (OR, 1.47; 95% CI, 1.32-1.63) were more prevalent in those with severe psoriasis than with mild psoriasis. The study was cross-sectional and therefore the directionality of the associations could not be determined. Multiple cardiovascular risk factors are associated with psoriasis. Cardiovascular risk factors that are key components of the metabolic syndrome are more strongly associated with severe psoriasis than with mild psoriasis.

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Epidermal Th22 and Tc17 cells form a localized disease memory in clinically healed psoriasis.

T. Talme, Stanley Cheuk, Maria Wikén … (2014)

Psoriasis is a common and chronic inflammatory skin disease in which T cells play a key role. Effective treatment heals the skin without scarring, but typically psoriasis recurs in previously affected areas. A pathogenic memory within the skin has been proposed, but the nature of such site-specific disease memory is unknown. Tissue-resident memory T (TRM) cells have been ascribed a role in immunity after resolved viral skin infections. Because of their localization in the epidermal compartment of the skin, TRM may contribute to tissue pathology during psoriasis. In this study, we investigated whether resolved psoriasis lesions contain TRM cells with the ability to maintain and potentially drive recurrent disease. Three common and effective therapies, narrowband-UVB treatment and long-term biologic treatment systemically inhibiting TNF-α or IL-12/23 signaling were studied. Epidermal T cells were highly activated in psoriasis and a high proportion of CD8 T cells expressed TRM markers. In resolved psoriasis, a population of cutaneous lymphocyte-associated Ag, CCR6, CD103, and IL-23R expressing epidermal CD8 T cells was highly enriched. Epidermal CD8 T cells expressing the TRM marker CD103 responded to ex vivo stimulation with IL-17A production and epidermal CD4 T cells responded with IL-22 production after as long as 6 y of TNF-α inhibition. Our data suggest that epidermal TRM cells are retained in resolved psoriasis and that these cells are capable of producing cytokines with a critical role in psoriasis pathogenesis. We provide a potential mechanism for a site-specific T cell-driven disease memory in psoriasis.

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Author and article information

Journal

Journal ID (nlm-ta): Int J Mol Sci

Journal ID (iso-abbrev): Int J Mol Sci

Journal ID (publisher-id): ijms

Title: International Journal of Molecular Sciences

Publisher: MDPI

ISSN (Electronic): 1422-0067

Publication date (Electronic): 05 September 2019

Publication date Collection: September 2019

Volume: 20

Issue: 18

Electronic Location Identifier: 4347

Affiliations

Department of Dermatology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan (M.Ki.) (J.S.), (M.K.) (M.O.)

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[* ]Correspondence: m01023kk@ 123456jichi.ac.jp ; Tel.: +81-285-58-7360

Article

Publisher ID: ijms-20-04347

DOI: 10.3390/ijms20184347

PMC ID: 6769762

PubMed ID: 31491865

SO-VID: abdc8980-7949-4a80-ad93-6ea1f1f5ac85

License:

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Risk Factors for the Development of Psoriasis

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Abstract

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Annual Reviews Child Development

Most cited references 120

Obesity in autoimmune diseases: not a passive bystander.

Prevalence of cardiovascular risk factors in patients with psoriasis.

Epidermal Th22 and Tc17 cells form a localized disease memory in clinically healed psoriasis.

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